Abstract Pediatric low grade gliomas (pLGG) are the most prevalent central nervous system tumors in children. The MAPK/ERK pathway drives tumorigenesis and provides a therapeutic target for precision therapies. KIAA1549-BRAF fusion and BRAF p.V600E mutation are the most common BRAF alterations in pLGG, but over 20 different BRAF-activating mutations have been reported in this population. We report a case of a pediatric patient with a tectal pilocytic astrocytoma with BRAF p.Thr599 duplication who has responded to targeted therapy with a selective BRAF inhibitor (dabrafenib) plus MEK inhibitor (trametinib) in the upfront and relapsed settings. A previously healthy 13-year-old female presented with two weeks of migraines, vision changes, emesis, and left eye deviation. MRI brain and spine demonstrated a 1.8 x 2.9 x 2.8 cm mass centered in the dorsal midbrain and pineal/tectal region with associated obstructive hydrocephalus. She underwent an endoscopic third ventriculostomy and tumor debulking. Pathologic examination confirmed a WHO grade1 pilocytic astrocytoma. Next-generation sequencing revealed a rare BRAF p.T599 duplication. After seven months of surveillance, MRI demonstrated tumor progression. The patient received two years of dabrafenib/trametinib therapy with great clinical and radiographic responses. However, migraines returned 6 months after completing therapy, and MRI demonstrated interval tumor growth (2.1 x 2 x 2.7 cm). She restarted dabrafenib/trametinib therapy and experienced immediate tumor shrinkage. She has had a durable clinical and radiographic response (2 x 1.9 x 1.4 cm) 11 months after restarting therapy. Although dabrafenib/trametinib combination therapy is indicated for pLGG harboring a BRAF p.V600E mutation, our report demonstrates the efficacy of this combination in a pediatric patient with a pilocytic astrocytoma harboring a BRAF p.T599 duplication, a type of non-V600E BRAF-mutated tumor, in both the upfront and relapsed settings. This has been previously reported in only one case of pediatric ganglioglioma in the upfront setting.
Memmott et al. (Fri,) studied this question.